Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), The ReproHealth Consortium ZUH, Zealand University Hospital, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Front Immunol. 2019 May 8;10:911. doi: 10.3389/fimmu.2019.00911. eCollection 2019.
Regulatory T cells, a subpopulation of suppressive T cells, are potent mediators of self-tolerance and essential for the suppression of triggered immune responses. The immune modulating capacity of these cells play a major role in both transplantation, autoimmune disease, allergy, cancer and pregnancy. During pregnancy, low numbers of regulatory T cells are associated with pregnancy failure and pregnancy complications such as pre-eclampsia. On the other hand, in cancer, low numbers of immunosuppressive T cells are correlated with better prognosis. Hence, maternal immune tolerance toward the fetus during pregnancy and the escape from host immunosurveillance by cancer seem to be based on similar immunological mechanisms being highly dependent on the balance between immune activation and suppression. As regulatory T cells hold a crucial role in several biological processes, they may also be promising subjects for therapeutic use. Especially in the field of cancer, cell therapy and checkpoint inhibitors have demonstrated that immune-based therapies have a very promising potential in treatment of human malignancies. However, these therapies are often accompanied by adverse autoimmune side effects. Therefore, expanding the knowledge to recognize the complexities of immune regulation pathways shared across different immunological scenarios is extremely important in order to improve and develop new strategies for immune-based therapy. The intent of this review is to highlight the functional characteristics of regulatory T cells in the context of mechanisms of immune regulation in pregnancy and cancer, and how manipulation of these mechanisms potentially may improve therapeutic options.
调节性 T 细胞是抑制性 T 细胞的一个亚群,是自身耐受的有力介质,对于抑制触发的免疫反应至关重要。这些细胞的免疫调节能力在移植、自身免疫性疾病、过敏、癌症和妊娠中都起着重要作用。在妊娠期间,调节性 T 细胞数量较少与妊娠失败和妊娠并发症(如子痫前期)有关。另一方面,在癌症中,抑制性 T 细胞数量较少与预后较好相关。因此,妊娠期间母体对胎儿的免疫耐受和癌症逃避宿主免疫监视似乎基于相似的免疫机制,高度依赖于免疫激活和抑制之间的平衡。由于调节性 T 细胞在几种生物学过程中起着关键作用,它们也可能是治疗用途的有前途的对象。特别是在癌症领域,细胞疗法和检查点抑制剂已经表明,免疫疗法在治疗人类恶性肿瘤方面具有非常有前途的潜力。然而,这些疗法通常伴随着不良的自身免疫副作用。因此,扩大对不同免疫场景中共享的免疫调节途径的复杂性的认识,对于改进和开发新的免疫治疗策略非常重要。本文的目的是强调调节性 T 细胞在妊娠和癌症中的免疫调节机制中的功能特征,以及这些机制的操纵如何可能改善治疗选择。